| 1. |
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| 2. |
- Berg, Johan, et al.
(författare)
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Structural changes at the surface of cytochrome c oxidase alter the proton-pumping stoichiometry
- 2020
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Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728 .- 1879-2650. ; 1861:2
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Tidskriftsartikel (refereegranskat)abstract
- Data from earlier studies showed that minor structural changes at the surface of cytochrome c oxidase, in one of the proton-input pathways (the D pathway), result in dramatically decreased activity and a lower proton-pumping stoichiometry. To further investigate how changes around the D pathway orifice influence functionality of the enzyme, here we modified the nearby C-terminal loop of subunit I of the Rhodobacter sphaeroides cytochrome c oxidase. Removal of 16 residues from this flexible surface loop resulted in a decrease in the proton-pumping stoichiometry to <50% of that of the wild-type enzyme. Replacement of the protonatable residue Glu552, part of the same loop, by an Ala, resulted in a similar decrease in the proton-pumping stoichiometry without loss of the O2-reduction activity or changes in the proton-uptake kinetics. The data show that minor structural changes at the orifice of the D pathway, at a distance of ~40 Å from the proton gate of cytochrome c oxidase, may alter the proton-pumping stoichiometry of the enzyme.
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| 3. |
- Bramhagen, Ann-Cathrine, et al.
(författare)
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Factors influencing iron nutrition among one-year-old healthy children in Sweden
- 2011
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Ingår i: Journal of Clinical Nursing. - : Blackwell Munksgaard. - 0962-1067 .- 1365-2702. ; 20:13-14, s. 1887-1894
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Tidskriftsartikel (refereegranskat)abstract
- Syfte och mål. Att beskriva möjliga sociala, nutritionella och biologiska faktorer som påverkar järnintag och järnstatus bland friska ett-åriga barn i södra Sverige. Bakgrund. Järnbrist är en av de viktigaste nutritionella bristtillstånden och ökar risken för försenad mental och motorisk utveckling. Barn utgör en riskgrupp relaterat till snabb tillväxt, vilken kräver ett relativt högt järnbehov. Design. En prospektiv studie. Metod. Slumpmässigt valda ett-åriga barn (n=90) och deras föräldrar deltog. Föräldrarna besvarade ett frågeformulär med sociodemografiska data samt barnets hälsa och nutrition under det första året. Barnets totala matintag och blodprover (hemoglobin, röda blodkroppars medelcellsvolum, S-ferritin och transferrin receptorer) samlades in. Resultat. Tjugosju procent av barnen hade ett järnintag som var under de Nordiska rekommendationerna på 8 mg/dag (NNR 2004). Välling och järnberikad gröt bidrog till 64 % av barnets totala järnintag. Partiell bröstmjölksuppfödning och låg utbildning bland mödrarna correlerade negativt med järnintag från tilläggskosten. Totalt, 10.3 % (n=9) av barnen hade tömda järnförråd (S-ferritin <12 ug/l) och 2.3 % (n=2) hade järnbrist med eller utan anemi (Hb<100g/l). Konklusion. Ett-åriga barn i Sverige kan utveckla järnbrist men information om järnrik föda kan förbättra järnstatus. Relevans till kliniskt arbete. Kunskap kring vilka faktorer som kan påverka barns järnintag och järnstatus kan förbättre de råd och den utbildning kring mat från barnhälsovården för att förebygga eller upptäcka järnbrist.
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| 4. |
- Dellgren, Goeran, et al.
(författare)
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Effect of once-per-daytacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial
- 2024
-
Ingår i: LANCET RESPIRATORY MEDICINE. - 2213-2600. ; 12:1, s. 34-44
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Tidskriftsartikel (refereegranskat)abstract
- Background Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation. Methods ScanCLAD is an investigator-initiated, open-label, multicentre, randomised, controlled trial in Scandinavia evaluating whether an immunosuppressive protocol based on anti-thymocyte globulin induction followed by tacrolimus (once per day), mycophenolate mofetil, and corticosteroids reduces the incidence of CLAD after de novo lung transplantation compared with a protocol using ciclosporin (twice per day), mycophenolate mofetil, and corticosteroids. Patients aged 18-70 years who were scheduled to undergo double lung transplantation were randomly allocated (1:1) to receive either oral ciclosporin (2-3 mg/kg before transplantation and 3 mg/kg [twice per day] from postoperative day 1) or oral tacrolimus (005-01 mg/kg before transplantation and 01-02 mg/kg from postoperative day 1). The primary endpoint was CLAD at 36 months post transplantation, determined by repeated lung function tests and adjudicated by an independent committee, and was assessed with a competing-risks analysis with death and re-transplantation as competing events. The primary outcome was assessed in the modified intention-to-treat (mITT) population, defined as those who underwent transplantation and received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02936505) and EudraCT (2015-004137-27). Findings Between Oct 21, 2016, and July 10, 2019, 383 patients were screened for eligibility. 249 patients underwent double lung transplantation and received at least one dose of study drug, and were thus included in the mITT population: 125 (50%) in the ciclosporin group and 124 (50%) in the tacrolimus group. The mITT population consisted of 138 (55%) men and 111 (45%) women, with a mean age of 552 years (SD 102), and no patients were lost to follow-up. In the mITT population, CLAD occurred in 48 patients (cumulative incidence 39% [95% CI 31-48]) in the ciclosporin group and 16 patients (13% [8-21]) in the tacrolimus group at 36 months post transplantation (hazard ratio [HR] 028 [95% CI 015-052], log-rank p<00001). Overall survival did not differ between groups at 3 years in the mITT population (74% [65-81] for ciclosporin vs 79% [70-85] for tacrolimus; HR 072 [95% CI 041-127], log-rank p=025). However, in the per protocol CLAD population (those in the mITT population who also had at least one post-baseline lung function test allowing assessment of CLAD), allograft survival was significantly better in the tacrolimus group (HR 049 [95% CI 026-091], log-rank p=0021). Adverse events totalled 1516 in the ciclosporin group and 1459 in the tacrolimus group. The most frequent adverse events were infection (453 events), acute rejection (165 events), and anaemia (129 events) in the ciclosporin group, and infection (568 events), anaemia (108 events), and acute rejection (98 events) in the tacrolimus group. 112 (90%) patients in the ciclosporin group and 108 (87%) in the tacrolimus group had at least one serious adverse event. Interpretation Immunosuppression based on use of tacrolimus once per day significantly reduced the incidence of CLAD compared with use of ciclosporin twice per day. These findings support the use of tacrolimus as the first choice of calcineurin inhibitor after lung transplantation.
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| 5. |
- Dufour, C, et al.
(författare)
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TNF-alpha and IFN-gamma are overexpressed in the bone marrow of Fanconi anemia patients and TNF-alpha suppresses erythropoiesis in vitro
- 2003
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 102:6, s. 2053-2059
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Tidskriftsartikel (refereegranskat)abstract
- In Fanconi anemia (FA) C mice tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have key roles in the pathogenesis of bone marrow failure. In FA subjects TNF-alpha was found to be increased in the serum and overproduced by patient-derived B-cell lines. In acquired aplastic anemia, a disease in which, similarly to FA, marrow failure occurs, TNF-alpha and IFN-gamma act as late mediators of the stem cell damage and are overexpressed in patient marrow lymphocytes. This study evaluated in marrow mononuclear cells (MNCs) of patients with FA, the expression of negative modulators of the hematopoiesis, such as TNF-alpha, IFN-gamma, macrophage inflammatory protein 1alpha (MIP-1alpha), and surface Fas ligand, and the role of TNF-alpha on FA erythropoiesis in vitro. TNF-alpha and IFN-gamma were significantly overexpressed in stimulated marrow MNCs of FA patients as compared to healthy controls. MIP-1alpha and Fas ligand were undetectable in patients and controls. In bone marrow cultures, the addition of anti-TNF-alpha increased the size and significantly increased the number of erythroid colony-forming units and erythroid burst-forming units grown from FA patients but not from healthy controls. This indicates that FA subjects have a marrow TNF-alpha activity that inhibits erythropoiesis in vitro. TNF-alpha has a relevant role in the pathogenesis of erythroid failure in FA patients.
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| 6. |
- Forsgren, Johan, et al.
(författare)
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Formation and adhesion of biomimetic hydroxyapatite deposited on titanium substrates
- 2007
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 3:6, s. 980-984
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Tidskriftsartikel (refereegranskat)abstract
- This study has been carried out to investigate the bioactivity of rutile and to deposit hydroxyapatite (HA) on heat-treated titanium through a biomimetic method. Biomimetic deposition of HA has gained large interest because of its low deposition temperature and good step coverage; however, it demands a substrate with bioactive properties. Commercially pure titanium is not bioactive but it can acquire bioactive properties through various surface treatments. In the present study, titanium plates were heat-treated at 800 °C to achieve rutile TiO2 surfaces. These samples were immersed in a phosphate-buffered saline solution for seven days in order to deposit a HA layer on the surface. The rutile TiO2 surfaces were found to be highly bioactive: after seven days of immersion, a layer of HA several micrometers thick covered the plates. The HA surfaces were confirmed by electron microscopy and X-ray diffraction. A scratch test was used to assess the adhesion of the HA coatings. This is a standard method to provide a measure of the coating-to-substrate adhesion and was found to be a useful method to test the thin HA coatings deposited on the bioactive surfaces. The critical pressure of the layer was estimated to be 2.4 ± 0.1 GPa.
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| 7. |
- Forsgren, Johan, et al.
(författare)
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Structural change of biomimetic hydroxyapatite coatings due to heat treatment
- 2007
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Ingår i: Journal of Applied Biomaterials & Biomechanics. - 1722-6899. ; 5:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- Biomimetic deposition of hydroxyapatite (HA) coatings on implants could be done for two reasons, one is to study their possible bioactivity, and one is to generate bioactive coatings on implants before implantation surgery to improve the osseointegration. Heat treatment of coated implants can be performed for several reasons, for example, to ensure coating sterility and to increase the adhesion. This paper describes the morphology and crystalline structure changes occurring due to the heat treatment of biomimetic HA coatings on rutile TiO2. Rutile TiO2 surfaces were produced on titanium (Ti) plates by heating at 800 C. Afterwards, these samples were immersed in a phosphate buffer saline solution for 7 days at 37 C in order to deposit HA coatings on their surfaces. These HA coatings were then either untreated or heat treated at 600 or 800 C for 1 hr. The coatings microstructural changes were studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cross-sectional TEM samples were produced using a sample preparation method based on focused ion beam microscopy (FIB). Rutile was found to be bioactive due to HA formation on the surface. The 600 C heat treatment of the HA coating changed its morphology, increased its grain size and also increased the porosity. At 800 C the coating was completely transformed to beta-TCP according to XRD. Sample preparation using FIB and TEM analysis proved to be a useful method for high-resolution analysis of biomimetic coatings in cross-section.
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| 8. |
- Funehag, Johan, et al.
(författare)
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Rock Excavation Cycle and Its Effect on Grouting
- 2019
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Ingår i: ISRM 9th Nordic Grouting Symposium. - : International Society for Rock Mechanics and Rock Engineering. - 9789517586481 ; , s. 47-59
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The drill and blast rock excavation cycle involves several processes that affects the grouting; vibration from drilling, borehole flushing, the blasting itself and water-loss measurements in boreholes. This research project focused on the effects of water-loss measurements, drilling (both vibration and flushing) and blasting on the grout and during the first five hours of the hardening process. A conceptual model was derived to explain what forces acts on the grout and how the forces can be interpreted in order to reveal how these forces effects the grout. The model suggests that the shear modulus of the grout is a key parameter for understanding the degradation of the grout. The different forces/stresses during an excavation effects the grout differently but the blasting is by far the most difficult process to describe. One starting point of the project is that the grout does not reinforce the rock and by that should not hinder the gas expansion. The blasting should generate new fractures around the blast hole and the gas will penetrate these cracks and finally the expansion of gases should cause fragmentation and movement in the rock mass. The paper describes the results from the field test and how the grout has been characterized using a rheometer. The field test was conducted in a short tunnel niche. The effects from the drill- and blast cycle were studied i.e. vibrations from drilling, boreholes flushing/water-loss measurements and vibrations from blasting. Five boreholes with a centrum distance of 1 m were chosen to be monitored, due to its hydraulic connectivity between the boreholes. Four of these boreholes were successfully grouted by following a grouting design and one borehole was left un-grouted and used for blasting. The effect on grouting in the rock mass from hole of blasting was measured using water-loss measurements in adjacent boreholes. One result of the field test is that the grout was not affected by the blasting under the circumstances used. Instead the study revealed that the water loss measurements affected the connected boreholes negatively.
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| 9. |
- Gantelius, Jesper, et al.
(författare)
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Magnetic bead-based detection of autoimmune responses using protein microarrays.
- 2009
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Ingår i: New biotechnology. - : Elsevier BV. - 1871-6784. ; 26, s. 269-276
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, a magnetic bead-based detection approach for protein microarrays is described as an alternative approach to the commonly used fluorescence-based detection system. Using the bead-based detection approach with applied magnetic force, it was possible to perform the detection step more rapidly as a result of the accelerated binding between the captured analyte in the microspot and the detection antibody, which was coupled to the magnetic beads. The resulting strong opacity shift on the microspots could be recorded with an ordinary flatbed scanner. In the context of autoimmunity, a set of 24 serum samples was analyzed for the presence of antibodies against 12 autoantigens using standard fluorescence and magnetic bead-based detection methods. Dynamic range, sensitivity, and specificity were determined for both detection methods. We propose from our findings that the magnetic bead-based detection option provides a simplified and cost effective readout method for protein microarrays.
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| 10. |
- Guldevall, Karolin, et al.
(författare)
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Imaging Immune Surveillance of Individual Natural Killer Cells Confined in Microwell Arrays
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11, s. e15453-
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Tidskriftsartikel (refereegranskat)abstract
- New markers are constantly emerging that identify smaller and smaller subpopulations of immune cells. However, there is a growing awareness that even within very small populations, there is a marked functional heterogeneity and that measurements at the population level only gives an average estimate of the behaviour of that pool of cells. New techniques to analyze single immune cells over time are needed to overcome this limitation. For that purpose, we have designed and evaluated microwell array systems made from two materials, polydimethylsiloxane (PDMS) and silicon, for high-resolution imaging of individual natural killer (NK) cell responses. Both materials were suitable for short-term studies (<4 hours) but only silicon wells allowed long-term studies (several days). Time-lapse imaging of NK cell cytotoxicity in these microwell arrays revealed that roughly 30% of the target cells died much more rapidly than the rest upon NK cell encounter. This unexpected heterogeneity may reflect either separate mechanisms of killing or different killing efficiency by individual NK cells. Furthermore, we show that high-resolution imaging of inhibitory synapse formation, defined by clustering of MHC class I at the interface between NK and target cells, is possible in these microwells. We conclude that live cell imaging of NK-target cell interactions in multi-well microstructures are possible. The technique enables novel types of assays and allow data collection at a level of resolution not previously obtained. Furthermore, due to the large number of wells that can be simultaneously imaged, new statistical information is obtained that will lead to a better understanding of the function and regulation of the immune system at the single cell level.
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| 11. |
- Kaznov, Viktor, et al.
(författare)
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Architecture and Safety for Autonomous Heavy Vehicles: ARCHER
- 2017
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Ingår i: Automated Driving. - Cham : Springer International Publishing. - 9783319318936 - 9783319318950 ; , s. 571-581
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Bokkapitel (refereegranskat)abstract
- Machines are converging towards autonomy. The transition is driven by safety, efficiency, environmental and traditional ‘robotics automation concerns’ (dirty, dull and dangerous applications). Similar trends are seen in several domains including heavy vehicles, cars and aircraft. This transition is, however, facing multiple challenges including how to gradually evolve from current architectures to autonomous systems, limitations in legislation and safety standards, test and verification methodology and human–machine interaction.
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| 12. |
- Khorshidi, Mohammad Ali, 1981-
(författare)
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Live Single Cell Imaging and Analysis Using Microfluidic Devices
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Today many cell biological techniques study large cell populations where an average estimate of individual cells’ behavior is observed. On the other hand, single cell analysis is required for studying functional heterogeneities between cells within populations. This thesis presents work that combines the use of microfluidic devices, optical microscopy and automated image analysis to design various cell biological assays with single cell resolution including cell proliferation, clonal expansion, cell migration, cell-cell interaction and cell viability tracking. In fact, automated high throughput single cell techniques enable new studies in cell biology which are not possible with conventional techniques.In order to automatically track dynamic behavior of single cells, we developed a microwell based device as well as a droplet microfluidic platform. These high throughput microfluidic assays allow automated time-lapse imaging of encapsulated single cells in micro droplets or confined cells inside microwells. Algorithms for automatic quantification of cells in individual microwells and micro droplets are developed and used for the analysis of cell viability and clonal expansion. The automatic counting protocols include several image analysis steps, e.g. segmentation, feature extraction and classification. The automatic quantification results were evaluated by comparing with manual counting and revealed a high success rate. In combination these automatic cell counting protocols and our microfluidic platforms can provide statistical information to better understand behavior of cells at the individual level under various conditions or treatments in vitro exemplified by the analysis of function and regulation of immune cells. Thus, together these tools can be used for developing new cellular imaging assays with resolution at the single cell level.To automatically characterize transient migration behavior of natural killer (NK) cells compartmentalized in microwells, we developed a method for single cell tracking. Time-lapse imaging showed that the NK cells often exhibited periods of high motility, interrupted with periods of slow migration or complete arrest. These transient migration arrest periods (TMAPs) often overlapped with periods of conjugations between NK cells and target cells. Such conjugation periods sometimes led to cell-mediated killing of target cells. Analysis of cytotoxic response of NK cells revealed that a small sub-class of NK cells called serial killers was able to kill several target cells. In order to determine a starting time point for cell-cell interaction, a novel technique based on ultrasound was developed to aggregate NK and target cells into the center of the microwells. Therefore, these assays can be used to automatically and rapidly assess functional and migration behavior of cells to detect differences between health and disease or the influence of drugs.The work presented in this thesis gives good examples of how microfluidic devices combined with automated imaging and image analysis can be helpful to address cell biological questions where single cell resolution is necessary.
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| 13. |
- Magnusson, Johan, 1976, et al.
(författare)
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Den stora vågen av digital kompetens
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Digital kompetens är en nödvändig resurs för ändamålsenlig digitalisering. Vi vet att digitaliseringen sätter fokus på medarbetares kompetens att hantera och designa digitala lösningar, men det saknas kunskapsunderlag om hur detta återspeglas i rekryteringsprocesser. Studien, baserad på analys av jobbannonser via öppna data, visar att efterfrågan på digital kompetens har fördubblats i offentlig sektor under perioden 2006-2019. Studien visar också att efterfrågan tydligt skiljer sig åt mellan kommuner, regioner, och myndigheter. Kommunsektorn uppvisar störst ökning av efterfrågan på digital kompetens. Medan denna sektor hade lägst efterfrågan 2006, uppvisar den högst efterfrågan i slutet av tidsspannet. Samtidigt har ökningen avstannat något inom myndighetssektorn, och avstannat helt inom regionsektorn från 2016. I jämförelse med utvecklingen inom privat sektor är efterfrågan på digital kompetens konstant lägre inom offentlig sektor. Under antagande om linjär utveckling kommer offentlig sektor vara ikapp privat sektor först år 2035.
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| 14. |
- Mankevich, Vasili, 1988, et al.
(författare)
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The Great Wave: The Increasing Demand for Digital Competence within the Public Sector
- 2023
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Ingår i: Information Polity. - 1570-1255. ; 28:3, s. 411-434
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Tidskriftsartikel (refereegranskat)abstract
- The increasing diffusion of digital government has led to numerous reports on both significant progress and failure in terms of digital transformation. Previous research highlights the role of digital competence as a pre-requisite for successful digital transformation, yet few studies have addressed the actual state of digital competence demand in the public sector. We study the development of digital competence demand in the Swedish public sector for the period 2006–2020. Utilizing a complete, open dataset of all job postings, we find that the digital competence demand in public sector recruitment has significantly increased. At the same time, the public sector lags behind the private in terms of digital competence demand. These findings are discussed from the perspectives of both the need for further research into human resource-related aspects of digital government and the national digital government policy. We also discuss the potential impact of disruptive events such as the COVID-19 pandemic and the 2009 financial crisis on digital competence demand.
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| 15. |
- Mohan, Naveen, et al.
(författare)
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ATRIUM - Architecting Under Uncertainty for ISO 26262 compliance
- 2017
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Ingår i: 2017 11TH ANNUAL IEEE INTERNATIONAL SYSTEMS CONFERENCE (SYSCON). - : IEEE. - 9781509046232 ; , s. 786-793
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Konferensbidrag (refereegranskat)abstract
- The ISO 26262 is currently the dominant functional safety standard for electrical and electronic systems in the automotive industry. The Functional Safety Concept sub-phase in the standard requires the Preliminary Architectural Assumptions (PAA) for allocation of functional safety requirements. This paper justifies the need for, and defines a process ATRIUM, for consistent design of the PAA. ATRIUM is subsequently applied in an industrial case study for a function enabling highly automated driving at one of the largest heavy vehicle manufacturers in Europe, Scania CV AB. The findings from this study, which contributed to ATRIUM's institutionalization at Scania, are presented. The benefits of ATRIUM include (i) a fast and flexible way to refine the PAA, and a framework to (ii) incorporate information from legacy systems into safety design and (iii) rigorously track and document the assumptions and rationale behind architectural decisions under uncertain information. The contributions of this paper are (i) the analysis of the problem (ii) the process ATRIUM and (iii) findings and the discussion from the case study at Scania.
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| 16. |
- Mohan, Naveen, et al.
(författare)
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System and Method for Controlling a Motor Vehicle to Drive Autonomously
- 2017
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Patent (populärvet., debatt m.m.)abstract
- A motor vehicle (MV) is controlled to drive autonomously in agreement with a nominal path in response to nominal control signals (NCS) from a bank of control units (110). Safety policies (P) are provided via a first data-interface unit (163). The safety policies (P) describe mission-related rules to be followed during operation of the motor vehicle (MV). The safety policies (P) are based on a safety case (SC) stipulating how the motor vehicle (MV) shall be controlled to meet a functional safety standard. A watch unit (160) receives sensor signals (SS) from the motor vehicle (MV), and based thereon repeatedly generates commands ({cmd}) to update the boundary conditions ({bc}) aiming at confining the nominal path within limits that are given by the sensor signals (SS) and the at least one safety policy (P). The bank of control units reads out the set of boundary conditions ({bc}) and controls the motor vehicle (MV) to move in such a manner that the nominal path satisfies the boundary conditions ({bc}), and is thus be considered to be safe.
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| 17. |
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| 18. |
- Paulsson, Johan O., et al.
(författare)
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Editorial Material: Absence of the BRAF V600E mutation in pheochromocytoma in JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, vol 39, issue 6, pp 715-716
- 2016
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Ingår i: Journal of Endocrinological Investigation. - : SPRINGER. - 0391-4097 .- 1720-8386. ; 39:6, s. 715-716
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose Pheochromocytomas (PCCs) are rare endocrine tumors originating from the adrenal medulla. These tumors display a highly heterogeneous mutation profile, and a substantial part of the causative genetic events remains to be explained. Recent studies have reported presence of the activating BRAF V600E mutation in PCC, suggesting a role for BRAF activation in tumor development. This study sought to further investigate the occurrence of the BRAF V600E mutation in these tumors. Methods A cohort of 110 PCCs was screened for the BRAF V600E mutation using direct Sanger sequencing. Results All cases investigated displayed wild-type sequences at nucleotide 1799 in the BRAF gene. Conclusions Taken together with all previously screened tumors up to date, only 1 BRAF V600E mutation has been found among 361 PCCs. These findings imply that the BRAF V600E mutation is a rare event in pheochromocytoma.
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| 19. |
- Ranta, Susanna, et al.
(författare)
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Extracorporeal Membrane Oxygenation Support in Children With Hematologic Malignancies in Sweden
- 2021
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Ingår i: Journal of Pediatric Hematology/Oncology. - : Wolters Kluwer. - 1077-4114 .- 1536-3678. ; 43:2, s. e272-e275
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Tidskriftsartikel (refereegranskat)abstract
- Background: Extracorporeal membrane oxygenation (ECMO) is used in severe respiratory and/or circulatory failure when conventional critical care fails. Studies on patients with hematologic malignancies on ECMO have shown contradictory results; immunosuppression and coagulopathy are relative contraindications to ECMO.Observations: This nationwide Swedish retrospective chart review identified 958 children with hematologic malignancies of whom 12 (1.3%) required ECMO support. Eight patients survived ECMO, 7 the total intensive care period, and 6 survived the underlying malignancy.Conclusions: ECMO may be considered in children with hematologic malignancy. Short-term and long-term survival, in this limited group, was similar to that of children on ECMO at large.
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| 20. |
- Ranta, S., et al.
(författare)
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High need for intensive care in paediatric acute myeloid leukaemia: A population-based study
- 2022
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:11, s. 2235-2241
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Tidskriftsartikel (refereegranskat)abstract
- Aim Risk of treatment-related life-threatening toxicity is high in childhood acute myeloid leukaemia (AML), and access to intensive care units (ICU) is crucial. We explored the ICU admission rate and outcome after intensive care in childhood AML in Sweden. Methods Patients diagnosed between 2008 and 2016 were identified from the Swedish Childhood Cancer Registry (SCCR), a national quality registry. Data from SCCR was cross-referenced with clinical questionnaire data from paediatric oncology centers and the Swedish Intensive Care Registry (SIR), another national quality registry. Results According to combined data, 46% of the children (58/126) were admitted to ICU, 17% (21/126) within 1 month from diagnosis. Overall, ICU mortality per admission was 12% and 6% during first-line treatment. There was a discrepancy between admission rate from the clinical questionnaires and SCCR (29%; 36/126 children) and SIR (44%; 55/126) All deaths during first-line treatment occurred at or after ICU care. Conclusion Although admission rate under AML treatment was high, the treatment-related mortality under first-line treatment was low. No child died under first-line treatment without admission to ICU, suggesting good availability. The discrepancy between the two registries, SCCR and SIR, highlights the need for future validation of registry data.
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| 21. |
- Ranta, Susanna, et al.
(författare)
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Icu admission in children with acute lymphoblastic leukemia in sweden: Prevalence, outcome, and risk factors
- 2021
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Ingår i: Pediatric Critical Care Medicine. - Philadelphia, PA, United States : Lippincott Williams & Wilkins. - 1529-7535 .- 1947-3893. ; 22:12, s. 1050-1060
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: Despite progress in the treatment of childhood acute lymphoblastic leukemia, severe complications are common, and the need of supportive care is high. We explored the cumulative prevalence, clinical risk factors, and outcomes of children with acute lymphoblastic leukemia, on first-line leukemia treatment in the ICUs in Sweden.DESIGN: A nationwide prospective register and retrospective chart review study.SETTING: Children with acute lymphoblastic leukemia were identified,and demographic and clinical data were obtained from the Swedish Childhood Cancer Registry. Data on intensive care were collected from the Swedish Intensive Care Registry. Data on patients with registered ICU admission in the Swedish Childhood Cancer Registry were supplemented through questionnaires to the pediatric oncology centers.PATIENTS: All 637 children 0-17.9 years old with acute lymphoblastic leukemia diagnosed between June 2008 and December 2016 in Sweden were included.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Twenty-eight percent of the children (178/637) were admitted to an ICU at least once. The Swedish Intensive Care Registry data were available for 96% of admissions (241/252). An ICU admission was associated with poor overall survival (hazard ratio, 3.25; 95% CI, 1.97-5.36; p ≤ 0.0001). ICU admissions occurred often during early treatment; 48% (85/178) were admitted to the ICU before the end of the first month of acute lymphoblastic leukemia treatment (induction therapy). Children with T-cell acute lymphoblastic leukemia or CNS leukemia had a higher risk of being admitted to the ICU in multivariable analyses, both for early admissions before the end of induction therapy and for all admissions during the study period.CONCLUSIONS: The need for intensive care in children with acute lymphoblastic leukemia, especially for children with T cell acute lymphoblastic leukemia and CNS leukemia, is high with most admissions occurring during early treatment.
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| 22. |
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| 23. |
- Remberger, Mats, et al.
(författare)
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Improved survival after allogeneic hematopoietic stem cell transplantation in recent years : A single-center study
- 2011
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 17:11, s. 1688-1697
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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| 24. |
- Reuterswärd, Philippa, et al.
(författare)
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Levels of human proteins in plasma as indicators for acute severe pediatric malaria
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundExisting low resource diagnostics for malaria infection suffer from sensitivity and specificity issues while lacking sufficient prognostic value. Identifying human host proteins could improve the possibilities to predict the risk of development of acute severe malaria. This will possible enable improved treatment and thereby lead to a decrease in mortality of malaria infected children. Furthermore, discovering host proteins with altered levels during active infection could generate leads to better understand host-parasite interaction.ResultsHere, we have analyzed a total of 541 pediatric plasma samples that were collected from community controls and individuals with mild or severe malaria in Rwanda. Protein profiles of these plasma samples were generated with an antibody-based suspension bead array containing 255 antibodies targeting 115 human proteins. We present 22 proteins with a strong discriminatory capacity (adjusted p-values below 10-19) for separating malaria cases from community controls. This panel of proteins contains among others acute phase proteins and proteins connected to cell adhesion and migration. Among these, three proteins showed lower plasma levels in the group of malaria-infected individuals compared to the control group. One of these proteins is the anti-adhesive secreted protein acidic and cysteine rich (SPARC) with possible connections to parasite cytoadhesion. A multi-protein panel of six proteins, including SPARC, could differentiate between controls and malaria cases with an AUC of 0.98. Furthermore, a panel of 37 proteins, including proteins associated to erythrocyte membranes, was identified as candidates for separation of mild and severe malaria patients (adjusted pvalues below 0.05).ConclusionThe herein identified set of human proteins has a significant discriminatory capacity between community controls and malaria cases. We also present proteins offering the possibility to enable stratification and risk prediction for the development of severe malaria. This constitutes an important set that could enable enhanced understanding and thereby also possibilities for better treatment of acute severe pediatric malaria.
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| 25. |
- Reuterswärd, Philippa, et al.
(författare)
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Levels of human proteins in plasma associated with acute paediatric malaria
- 2018
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Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts. Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values<0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values<10(-14)) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values<0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria. Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.
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| 26. |
- Ringdén, Olle, et al.
(författare)
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Cytokine levels following allogeneic hematopoietic cell transplantation : a match-pair analysis of home care versus hospital care
- 2021
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Ingår i: International Journal of Hematology. - : Springer Nature. - 0925-5710 .- 1865-3774. ; 113:5, s. 712-722
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Tidskriftsartikel (refereegranskat)abstract
- Following allogeneic hematopoietic cell transplantation (HCT), patients living near the hospital were treated at home instead of in isolation in the hospital. We analyzed cytokines using Luminex assays for the first 3 weeks after HCT and compared patients treated at home (n = 42) with matched patients isolated in the hospital (n = 37). In the multivariate analysis, patients treated at home had decreased GM-CSF, IFN-γ (p < 0.01), IL-13, IL-5 (p < 0.05), and IL-2 (p < 0.07). Bloodstream infections, anti-thymocyte globulin, G-CSF treatment, immunosuppression, reduced-intensity conditioning (RIC), related vs. unrelated donors, and graft source affected various cytokine levels. When patients with RIC were analyzed separately, home care patients had reduced G-CSF (p = 0.04) and increased vascular endothelial growth factor (VEGF, p = 0.001) at 3 weeks compared with hospital care patients. Patients with low GM-CSF (p < 0.036) and low IFNγ (p = 0.07) had improved survival. Acute GVHD grades III–IV was seen in 7% and 16% of home care and hospital care patients, respectively. One-year transplantation-related mortality was 7% and 16% and survival at 5 years was 69% and 57% in the two groups, respectively. To conclude, patients treated in the hospital showed varying increased levels of GM-CSF, IFN-γ, IL-13, G-CSF, IL-5, and IL-2 and decreased VEGF, which may contribute to acute GVHD.
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| 27. |
- Svahn Gustafsson, Sofia
(författare)
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Characterization of HCV Protease Inhibitors : Inhibition and Interaction Studies with Applications for Drug Discovery
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, different approaches based on inhibition and interactions studies, have been used to characterize inhibitors of the non-structural protein 3 (NS3) from the hepatitis C virus (HCV). This involves identification of enzyme inhibitory effects and characterization of interaction mechanisms and kinetics, as well as effects on replication in a cell based system and serum protein binding. All this information contributes to HCV drug discovery.By using an inhibition assay it was possible to evaluate the effects of NS3 protease inhibitors, tested or used in the clinic, on NS3 variants, representing different model systems often used for drug discovery. This study illustrates the importance of accounting for differences in catalytic properties in comparative analyses, for making relevant interpretations of inhibition data. An SPR biosensor-based assay expanded the first study, and provided kinetic and mechanistic information, by direct interaction analyses of the inhibitors. It revealed significant differences between the different genotypes and model systems, and provided data that can be used to better understand the efficacy of inhibitors.Additionally, novel NS3 protease inhibitors were evaluated with respect to their potential to interfere with protease activity, their sensitivity to resistant mutants and effect on HCV replication. The most potent compounds were also characterized by their bioavailability, solubility and metabolic stability. This provides information for design of improved NS3 protease inhibitors, suggesting potential peptidomimetic structures for the backbone as well as for peptide substituents. These modification strategies allowed inhibitors to be truncated and less peptide-like, still with retained inhibitory effect.A new strategy for analysis of serum protein binding, of importance for drug distribution was also developed. By defining and using the concept of binding efficiency, serum protein interactions of moderate affinity, as described by rapid kinetics, were characterized. This strategy is also applicable for analysis of low affinity interactions.Taken together, all these studies provide knowledge and strategies for HCV drug discovery, and by using this information we might take a step closer to the final goal, which is to eradicate HCV.
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| 28. |
- Svahn, Johan, et al.
(författare)
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Different quantities and quality of fat in milk products given to young children: effects on long chain polyunsaturated fatty acids and trans fatty acids in plasma.
- 2002
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Ingår i: Acta Pædiatrica. - 1651-2227. ; 91:1, s. 20-29
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Tidskriftsartikel (refereegranskat)abstract
- In this study we compared plasma contents of long-chain polyunsaturated fatty acids (LC-PUFAs) and trans fatty acids in triglycerides (TG), phospholipids (PL) and cholesterolesters (CE) in young children fed milk diets containing different amounts of linoleic (LA) and alpha-linolenic acid (ALA). Because the diets differed in vitamin A and E content, plasma concentrations of vitamin A and E were also studied. Thirty-seven 1-y-old children were randomly assigned to one of four feeding groups: (1) low-fat milk (LF) (1.0 g cow's milk fat/dL); (2) standard-fat milk (SF) (3.5 g cow's milk fat/dL); (3) partially vegetable fat milk (PVF) (3.5 g fat/dL; 50% vegetable fat from rapeseed oil, 50% milk fat); and (4) full vegetable fat milk (FVF) (3.5 g fat/dL; 100% vegetable fat from palm-, coconut- and soybean oil). We found higher amounts of plasma LA in the FVF group than in the LF and SF groups (p < 0.001) and higher amounts of ALA in the PVF group than in the SF (p < 0.001 in TGs, p < 0.05 in CEs) and LF (p < 0.01 in PLs and CEs, p < 0.05 in TGs) groups. However, amounts of plasma arachidonic acid (AA) were similar between groups as well as the amounts of docosahexaenoic acid (DHA) in CEs and PLs. Total trans FAs were lower in CEs in the PVF and FVF groups than in the SF group (p < 0.05 SF vs PVF; p < 0.01 SF vs FVF). Plasma concentrations of alpha-tocopherol were higher in the FVF group than in the other groups (p < 0.05 FVF vs SF, p < 0.01 FVF vs SF and PVF). Conclusion: Children consuming milk diets containing high amounts of vegetable fat present with higher plasma LA and ALA without any effects on amounts of plasma LC-PUFA. The plasma LC-PUFA status is not adversely affected by a low-fat milk diet. AHA and DHA in plasma are not affected by the diets studied, presumably because 15-mo-old children may be able to compensate for dietary influences through endogenous LC-PUFA metabolism.
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| 29. |
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| 30. |
- Svahn, Johan
(författare)
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Nutrition in the second year of life. Effects of different milk compositions on dietary intakes, growth and metabolism.
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the diet for young children, whole cow´s milk is the major contributor of calories, protein and saturated fat, but it supplies little iron and polyunsaturated fat. Although several recommendations exist for the composition of formula, recommendations for the composition of milk for young children are lacking. We investigated if milk with modified fat-, protein-, and iron content aimed at young children could be advantageous to whole cow´s milk. Therefore, children were fed one of four different milk diets: standard fat cow´s milk; low fat cow´s milk or iron fortified, protein reduced cow´s milk with either 50% or 100% vegetable fat. From 12 to 18 months of age, dietary intakes, growth and indices of fat-, protein-, and iron metabolism were compared between the groups. We found similar energy intakes and growth in all groups despite differences in energy content in the milk used. Children given iron fortified, protein reduced milk with 50 or 100% vegetable fat had saturated fat intake around 12 % of energy; polyunsaturated fat intake around 6% of energy, both verified in plasma fatty acid contributions; recommended iron intake and protein intake closer to recommendations. Children fed low fat milk had fat intakes below 30% of energy. Further, children fed whole cow´s milk showed saturated fat intakes of around 19% of energy, signs of weaker development of iron stores and indices of protein metabolism indicating unnecessarily high protein intakes. The differences in intakes of polyunsaturated fat had no major effect on plasma long-chain polyunsaturated fatty acid contributions. We found that a reduction of saturated fat intake and recommended protein and iron intake is difficult to achieve without modifications in the fat, protein and iron compositions of whole cow´s milk. Therefore, we propose that a recommendation of fat quality composition and protein and iron content in milk for young children should be developed.
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